TGFβ signalling: a nexus between inflammation, placental health and preeclampsia throughout pregnancy

Human Reproduction Update, Год журнала: 2024, Номер 30(4), С. 442 - 471

Опубликована: Март 22, 2024

Abstract BACKGROUND The placenta is a unique and pivotal organ in reproduction, controlling crucial growth cell differentiation processes that ensure successful pregnancy. Placental development tightly regulated dynamic process, which the transforming factor beta (TGFβ) superfamily plays central role. This family of pleiotropic factors heavily involved regulating various aspects reproductive biology, particularly trophoblast during first trimester TGFβ signalling precisely regulates invasion transition from cytotrophoblasts to extravillous trophoblasts, an epithelial-to-mesenchymal transition-like process. Later pregnancy, ensures proper vascularization angiogenesis placental endothelial cells. Beyond its role trophoblasts cells, contributes polarization function decidual macrophages by promoting maternal tolerance semi-allogeneic foetus. Disturbances early have been associated with several pregnancy complications, including preeclampsia (PE) one severe complications. Emerging evidence suggests pathogenesis PE, thereby offering potential target for intervention human placenta. OBJECTIVE AND RATIONALE comprehensive review aims explore elucidate roles major members superfamily, TGFβs, bone morphogenetic proteins (BMPs), activins, inhibins, nodals, (GDFs), context function. focusses on their interactions within types placenta, namely immune both normal pregnancies complicated PE throughout SEARCH METHODS A literature search was carried out using PubMed Google Scholar, searching terms: ‘TGF preeclampsia’, ‘pregnancy TGF signalling’, ‘preeclampsia tgfβ’, bmp’, gdf’, activin’, ‘endoglin pregnancy’, ‘tgfβ ‘bmp ‘gdf ‘activin ‘Hofbauer tgfβ ‘placental ‘endothelial cells ‘endothelium ‘trophoblast Smad’, development’, ‘TGFβ function’, dysfunction ‘vascular remodelling TGFβ’, ‘inflammation ‘immune response NK cells’, tregs’, ‘NK ‘Tregs preeclampsia’. Only articles published English until 2023 were used. OUTCOMES understanding interconnected functions main provides valuable insights into essential foetus By orchestrating invasion, vascularization, tolerance, tissue remodelling, ligands contribute functioning healthy maternal–foetal interface. However, dysregulation has implicated where shallow defective vascular decreased uteroplacental perfusion, observed are all affected altered signalling. WIDER IMPLICATIONS important implications research clinical practice. Further investigation required understand underlying mechanisms, different regulation under pathophysiological conditions, order discover new therapeutic targets. Distinguishing between clinically manifested subtypes studying holistically step. To put this knowledge practice, pre-clinical animal models combined technologies needed. may also lead improved identify targets, ultimately improving outcomes reducing burden PE.

Язык: Английский

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Trophoblast Fusion in Hypertensive Disorders of Pregnancy and Preeclampsia

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 2859 - 2859

Опубликована: Март 21, 2025

Trophoblast fusion into the multinucleated syncytiotrophoblast (SCT) appears as an inescapable feature of placentation in mammals and other viviparous species. The trophoblast cells underlying syncytium are considered a reservoir for restoration aging peripheric structure. transition from trophoblasts to SCTs has be tightly regulated, could altered by genetic anomalies or environmental exposure. resulting defective placental function one causes major diseases, such preeclampsia (PE) Intra-Uterine Growth Restriction (IUGR). This review attempts take stock current knowledge about mechanisms their deregulations.

Язык: Английский

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Oxidative stress induces release of mitochondrial DNA into the extracellular space in human placental villous trophoblast BeWo cells

AJP Cell Physiology, Год журнала: 2024, Номер 326(6), С. C1776 - C1788

Опубликована: Май 13, 2024

Circulating cell-free mitochondrial DNA (ccf-mtDNA) is an indicator of cell death, inflammation, and oxidative stress. ccf-mtDNA in pregnancies with placental dysfunction differs from that healthy pregnancies, the direction this difference depends on gestational age method mtDNA quantification. Reactive oxygen species (ROS) trigger release mtDNA, yet it unknown whether trophoblast cells response to stress, a common feature pathology. We hypothesized stress would induce death cells. BeWo were treated antimycin A (10-320 µM) or rotenone (0.2-50 multiplex real-time quantitative PCR (qPCR) assay was used quantify nuclear membrane-bound, non-membrane-bound, vesicle-bound forms culture supernatants lysates. Treatment increased ROS (

Язык: Английский

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Comparative analysis of the syncytiotrophoblast in placenta tissue and trophoblast organoids using snRNA sequencing

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 4, 2024

Abstract The outer surface of chorionic villi in the human placenta consists a single multinucleated cell called syncytiotrophoblast (STB). unique cellular ultrastructure STB presents challenges deciphering its gene expression signature at single-cell level, as contains billions nuclei cell. There are many gaps understanding molecular mechanisms and developmental trajectories involved formation differentiation. To identify underlying control STB, we performed comparative nucleus (SN) (SC) RNA sequencing on placental tissue tissue-derived trophoblast organoids (TOs). We found that SN was essential to capture population from both TOs. Differential pseudotime analysis TO-derived identified three distinct nuclear subtypes reminiscent those recently vivo . These included juvenile exhibited CTB marker expression, enriched genes oxygen sensing, finally subtype transport GTPase signaling molecules. Notably, suspension culture conditions TOs restore native orientation (STB out ) showed elevated canonical markers pregnancy hormones, along with greater proportion specializing signaling, compared cultivated an inverted polarity ). Gene regulatory novel differentiation conserved TOs, including chromatin remodeler RYBP, STB-specific protein expression. CRISPR/Cas9 knockout RYBP did not impact cell-cell fusion; however, bulk revealed downregulation hormone CSH1 upregulation multiple associated oxygen-sensing subtype. Finally, signatures amongst first trimester tissue, full-term identifying commonalities but also notable variability across each sample type. This indicates is responsive environmental context. Our findings emphasize utility accurately model observed , offering versatile platform for unraveling governing functions biology disease.

Язык: Английский

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Epigenetic dynamics of partially methylated domains in human placenta and trophoblast stem cells

BMC Genomics, Год журнала: 2024, Номер 25(1)

Опубликована: Ноя. 6, 2024

The placenta is essential for nutrient exchange and hormone production between the mother developing fetus serves as an invaluable model epigenetic research. Most studies of human have used whole placentas from term pregnancies identified presence partially methylated domains (PMDs). However, origin these domains, which are typically absent in most somatic cells, remains unclear placental context. Using whole-genome bisulfite sequencing analysis histone H3 modifications, we generated profiles cytotrophoblasts during first trimester at term, well trophoblast stem cells. Our study focused specifically on PMDs. We found that genomic regions likely to form PMDs resistant global DNA demethylation trophectoderm reprogramming, arise through a slow methylation process within condensed chromatin near nuclear lamina. In addition, significant differences modifications findings suggest spatiotemporal features shape megabase-scale patterns, including PMDs, highlight distinct These advance our understanding biology provide basis further research into development related diseases.

Язык: Английский

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Tire rubber-derived contaminants 6PPD and 6PPD-quinone reduce attachment and outgrowth of trophoblast spheroids onto endometrial epithelial cells

Ecotoxicology and Environmental Safety, Год журнала: 2025, Номер 290, С. 117744 - 117744

Опубликована: Янв. 1, 2025

N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), a synthetic additive widely used in the rubber industry, and its oxidized product 6PPD-quinone (6PPDQ), have garnered widespread attention as an emerging hazardous chemicals owing to their potential detrimental effects on aquatic ecosystem human health. The of 6PPD 6PPDq female reproductive tract, especially embryo implantation, remain unknown were investigated this study. We spheroid attachment outgrowth models BeWo trophoblastic spheroids Ishikawa cells surrogates for blastocyst endometrial epithelium, respectively. Treatment with up 48 h decreased viability dose- cell line-dependent manner (20-100 μM 10-100 6PPDQ both lines). At noncytotoxic concentration, exposure 1 10 reduced further inhibited invasion epithelial monolayer. A similar result was observed 6PPDQ-exposed groups. Gene expression profiling 6PPD- revealed that differentially regulated panel transcript markers toward overall downregulation receptivity invasion. study provides first proof adverse trophoblast during window warranting need vivo clinical studies.

Язык: Английский

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Temporal Myc dynamics permit mitotic bypass, promoting polyploid phenotypes

Cancer Letters, Год журнала: 2025, Номер 613, С. 217526 - 217526

Опубликована: Фев. 3, 2025

Язык: Английский

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Culture of cryopreserved first trimester placental tissues to study syncytial renewal

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 10, 2025

Ex vivo studies with first trimester placental tissues are crucial for understanding human development, and culturing villi in floating conditions is vital to mimic the natural setting. Moreover, being able cryopreserve these scarce materials ex would open unprecedented avenues, as they very limited research need culture freshly adds further hurdles while limiting efficient use. Here we showed that hanging drop method a simple yet effective approach villi. We also revealed functional units of early-stage placenta can be cryopreserved culturing, frozen-thawed regenerate syncytial layer following denudation. illustrated utility study syncytialization, validating importance HtrA4 process which was shown previously cell models. These represent significant new knowledge field biology.

Язык: Английский

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Ultrasound Evaluation of the Changes of Ophthalmic Artery Doppler and Optic Nerve Sheath in Pregnant Women With FGR

Journal of Ultrasound in Medicine, Год журнала: 2025, Номер unknown

Опубликована: Фев. 11, 2025

Objectives This study aimed to compare changes in ultrasonic Doppler parameters, particularly the peak ratio (PR) of ophthalmic artery (OA) and optic nerve sheath diameter (ONSD), pregnancies complicated by fetal growth restriction (FGR). Furthermore, it sought evaluate differences these parameters across various subgroups analyze cut‐off value PR for predicting delivery within 1 week FGR. Methods A total 62 pregnant women mid‐to‐late stages gestation were enrolled, comprising 31 participants FGR group control group. The general conditions, pregnancy outcomes, OA, ONSD compared between two groups. Comparative analysis was performed investigate OA subgroups. predictive assessed using area under receiver operating characteristic curve. Results significantly elevated group, demonstrating a statistically significant difference. threshold 0.565, with sensitivity 0.88 specificity 0.58. Conclusions is increased may serve as reliable predictor

Язык: Английский

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A Locus Control Region Generates Distinct Active Placental Lactogen And Inactive Growth Hormone Gene Domains In Term Placenta That Are Disrupted With Obesity

Placenta, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

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